Pulmonary infections continue to cause considerable morbidity and are a major contribution to the shortened life span of patients with cystic fibrosis. Improvements in the quality and duration of life have resulted from treatment of established infections, along with improvements in nutrition and general health care in these patients. Nevertheless, persistence of infection, superinfection and progressive pulmonary damage are of major concern in this disease. The research is aimed at early events in the development of pulmonary infection in patients with cystic fibrosis. We postulate that damage consequent to bacterial endobronchitis contributes to the subsequent development of persistent sputum colonization and chronic and recurrent bronchitis and bronchopneumonia. We further suggest that early prevention of these initial bacterial pulmonary infections may retard subsequent progressive bronchitis and colonization by more opportunistic organisms. The study plan, therefore, is a multi-center, placebo-controlled, double-blind randomized evaluation of continuous long-term cephalexin prophylaxis versus placebo in newly disgnosed infants with cystic fibrosis. Infants are chosen in an effort to compare a homogeneous group of patients and ones in whom progressive pulmonary damage and recurrent endobronchial infections are not yet established. If antibiotic prophylaxis is effective, the development of pulmonary infection will be delayed or prevented. This will be assessed by clinical and laboratory parameters. The latter will include morbidity, physical growth, evaluation of pulmonary function, and microbiologic criteria. Additional information will be derived about the tolerance and toxicity of long-term cephalexin administration and its effects on the bacterial ecology of respiratory secretions in patients with cystic fibrosis. The multi-center collaborative design will also unify the cystic fibrosis clinical research community in an unprecedented fashion, so that this study may serve as a prototype for other investigations. It is anticipated the clinician will be left with a clear answer about the question of whether continuous antibiotic prophylaxis is indicated in the newly diagnosed patient with cystic fibrosis.